In recent years, investigations into the biochemical pharmacology of ethanol have focussed on the role of tetrahydroisoquinoline (TIQ) alkaloids (which are condensation products of acetaldehyde, the primary metabolite of ethanol, with endogenous catecholamines) as possible mediators of the behavioral, autonomic, and teratogenic effects of ethanol. Both in vitro and acute in vivo studies have demonstrated the biosynthesis of these TIQs in animals and in man. Speculations on the role of TIQs in the development of physical dependence to alcohol have received considerable attention. This investigation addresses itself to the following questions: (1) Are TIQs (such as salsolinol) formed in vivo under condition of physical dependence to alcohol, without specific pharmacological manipulations of the experimental model? A gas-chromatographic/electron-capture assay for salsolinol developed in our laboratory could not detect nanogram quantities of salsolinol in brains of ethanol-dependent mice. The question will be re-examined using a radioenzymatic assay capable of detecting picogram quantities of salsolinol. (2) Do TIQs cross the placenta and do they affect fetal development causing teratogenicity? This question will be again examined using the radioenzymatic assay for salsolinol developed in our laboratory. (3) Is alcohol teratogenicity the result of interference with vitamin A metabolism by alcohol? This question will be examined by an assay developed in our laboratory for measuring five different vitamin A metabolites.